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CaM Kinase Co‐localization and Regulation of p53 in Breast Cancer Cells
Author(s) -
Coblentz Cody,
Geck Renee,
Schmitt John M
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.644.9
Subject(s) - phosphorylation , kinase , cancer research , chemistry , cancer cell , cell growth , microbiology and biotechnology , biology , cancer , medicine , biochemistry
The Ca2+/calmodulin dependent kinases (CaM KK and CaM KI) have been implicated in several types of cancer including breast cancer. CaM KK and CaM KI are known to control several transcription factors. CaM KI has also been shown to bind and phosphorylate the cell cycle protein p27 to promote cell cycle progression. Interestingly, the tumor suppressor p53 contains a possible CaM KI phosphorylation site at S366. The aim of this study was to investigate CaM KI‐p53 association, CaM KI targeted phosphorylation (S366) of p53, and subsequent breast cancer growth in both MDA‐MB‐231 and MCF‐7 cells. GST pull‐downs, immunoprecipitation, as well as confocal microscopy of endogenous proteins showed that CaM KI associates with p53 phosphorylated at S366. Treatment of MCF‐7 and MDA‐MD‐231 cells with estrogen (E2) and carbachol respectively, increases the association of CaM KI‐p53 and S366 phosphorylation. siRNA knockout of CaM KI blocked E2 and carbachol‐induced S366 phosphorylation and constitutively active CaM KK increased p53 phosphorylation in breast cancer cells. Interestingly, both E2 and carbachol increased MCF‐7 and MDA‐MD‐231 cell growth respectively through CaM Kinase and p53. In summary, our data suggests that CaM KI binds and phosphorylates p53 in MCF‐7 and MDA cells, and that E2 and carbachol stimulate cell growth through a novel CaM KI‐p53 pathway. Support or Funding Information The Paul K. and Evalyn E. C. Richter Memorial Fund. This work was supported through a Life Science grant from the M.J. Murdock Charitable Trust to J.M.S. grant #2011267